Unifying Frequency Combs in Active and Passive Cavities: Temporal Solitons in Externally Driven Ring Lasers.

Frequency combs have become a prominent research area in optics. Of particular interest as integrated comb technology are chip-scale sources, such as semiconductor lasers and microresonators, which consist of resonators embedding a nonlinear medium either with or without population inversion. Such active and passive cavities were so far treated distinctly. Here we propose a formal unification by introducing a general equation that describes both types of cavities. The equation also captures the physics of a hybrid device-a semiconductor ring laser with an external optical drive-in which we show the existence of temporal solitons, previously identified only in microresonators, thanks to symmetry breaking and self-localization phenomena typical of spatially extended dissipative systems.

Return to sport activities after medial displacement calcaneal osteotomy and flexor digitorum longus transfer.

PURPOSE: Medial displacement calcaneal osteotomy with flexor digitorum longus transfer is a common treatment for the management of the adult flatfoot associated with posterior tibial tendon dysfunction. In the literature, there is a paucity of information regarding the ability of patients to return to sport and recreational activities after this surgical procedure. The purpose of this retrospective clinical study was to assess the rate and type of athletic activities that patients participated in before and after medial displacement calcaneal osteotomy with flexor digitorum longus transfer. METHODS: A consecutive series of 42 patients with a mean age at surgery of 41 years (range 19-74 years) was evaluated with a minimum follow-up of 24 months (range 18-31 months). Pre- and post-operative sporting activities were assessed. At final follow-up, patients were asked to complete a Sports Athlete Foot and Ankle Score (SAFAS). Each patient was also evaluated with weight-bearing radiographs of the foot before surgery and at final follow-up. RESULTS: Preoperatively, 27 of 42 (64.3 %) patients were engaged in athletic activities, participating in an average of 1.4 h/week (range 0-6 h/week); post-operatively, 36/42 (85.7 %) participated in sport and recreational activities for an average of 3.5 h/week (range 0-15 h/week). Meary's angle improved significantly from 11.5 ± 6.2 degrees preoperatively to 7.0 ± 5.7 degrees at final follow-up (p < 0.01); calcaneal pitch improved significantly from 16.5 ± 4.6 degrees to 19.0 ± 5.0 degrees (p < 0.01). At final follow-up, patients demonstrated good SAFASs in symptom tolerance (86.4 %), pain tolerance (89.0 %), daily living performance (96.1 %), and sports performance (86.7 %). CONCLUSION: The majority of patients returned to sports and recreational activity after medial displacement calcaneal osteotomy and flexor digitorum longus for the treatment of adult flatfoot associated with posterior tibial tendon dysfunction. LEVEL OF EVIDENCE: III.

Epidemiological and clinical characteristics of patients attending STI clinics in Tuscany, Italy: a multicenter report on new infections in 2011.

AIM: The aim of this study was to assess the demographic, behavioral and clinical features associated with newly diagnosed sexually transmitted infections (STIs) among attendees from four STI Clinics during 2011 in Tuscany, Central Italy. METHODS: Electronic and non-electronic medical records of attendees were reviewed to collect socio-demographical and anamnestic characteristics of patients, and to assess the annual incidence and distribution of STIs. RESULTS: The study included 1293 subjects, for a total number of 1394 newly diagnosed STIs. The male/female ratio was about 2:1, and Italian nationality accounted for 84.1% of the sample. MSM represented the 25.9% of the male population. Condom use was very poor in the large majority of our sample. Genital warts and non-gonococcal cervicitis and urethritis were the most frequent STIs. Anamnestic STIs were recorded in 350 subjects. When stratified for sexual preference, men who have sex with men were found at four to ten fold increased risk for syphilis, gonorrhoeae and HIV infection. New diagnoses of syphilis, gonorrhoea, urethritis and molluscum were strictly associated with infections by the same pathogens in the past (re-infections). CONCLUSIONS: Results show that STIs in Tuscany involve a mixed young to adult population, composed by both heterosexual and homosexual subjects who practice unprotected sex and do not seem to be conscious of the associated risks, as demonstrated by the high rates of coinfections and reinfections. These findings reinforce the need for greater education and prevention efforts for HIV and other STIs among the Tuscan population.

Steroid injections in the treatment of humeral unicameral bone cysts: long-term follow-up and review of the literature.

BACKGROUND: Retrospective evaluation of long-term effectiveness of the steroid injections treatment in patients with unicameral bone cysts (UBC). METHODS: From January 1993 to April 2005, 23 children affected by proximal humeral UBC were evaluated according to the Neer-Cole classification system and treated with serial methylprednisolone acetate's injections. The patients were followed up at 1, 3, 6 and 12 months and then every year until the adolescence. RESULTS: After treatment, in 15 out of 23 patients (65.2%), the humeral cysts were referred, respectively, as Grade 1 and in four as Grade 2. In 4 patients, a refracture occurred. Statistical analysis showed an overall good response in 82.6% of patients at the end of the follow-up. Minor complication including skin discoloration accounted for 13.04%. CONCLUSIONS: The steroid injections showed to be an alternative excellent treatment for UBC, with complete healing of the lesions in the majority of cases. This procedure is not expensive, mini-invasive, with low surgical risk and short hospitalization.

Probiotic interventions promote metabolic health in high fat-fed hamsters in association with gut microbiota and endocannabinoidome alterations.

Probiotics represent a promising tool to improve metabolic health, including lipid profiles and cholesterol levels. Modulation of the gut microbiome and the endocannabinoidome - two interrelated systems involved in several metabolic processes influenced by probiotics - has been proposed as a potential mechanism of action. This study establishes the impact of probiotics on metabolic health, gut microbiota composition and endocannabinoidome mediators in an animal model of hypercholesterolaemia. Syrian hamsters were fed either a low-fat low-cholesterol or high-fat high-cholesterol (HFHC) diet to induce hypercholesterolaemia and gavaged for 6 weeks with either Lactobacillus acidophilus CL1285, Lactiplantibacillus plantarum CHOL-200 or a combination of the two. Globally, probiotic interventions ameliorated, at least partially, lipid metabolism in HFHC-fed hamsters. The interventions, especially those including L. acidophilus, modified the gut microbiota composition of the small intestine and caecum in ways suggesting reversal of HFHC-induced dysbiosis. Several associations were observed between changes in gut microbiota composition and endocannabinoidome mediators following probiotic interventions and both systems were also associated with improved metabolic health parameters. For instance, potential connexions between the Eubacteriaceae and Deferribacteraceae families, levels of 2­palmitoylglycerol, 2­oleoylglycerol, 2­linoleoylglycerol or 2­eicosapentaenoylglycerol and improved lipid profiles were found. Altogether, our results suggest a potential crosstalk between gut microbiota and the endocannabinoidome in driving metabolic benefits associated with probiotics, especially those including L. acidophilus, in an animal model of hypercholesterolaemia.

In vitro activity and in vivo efficacy of tigecycline alone and in combination with daptomycin and rifampin against Gram-positive cocci isolated from surgical wound infection.

The aim of this work was to determine the in vitro activity of tigecycline and its bactericidal effect for a large number of Gram-positive cocci, as well as to investigate its in vitro interaction with six clinically used antibiotics. In vivo, a wound model was established through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 10(7) colony-forming units (CFU) of Staphylococcus aureus or Enterococcus faecalis. For each bacterial strain, the study included an infected or non-infected group that did not receive any treatment, three groups singly treated with tigecycline, rifampin, and daptomycin, and two groups that received tigecycline treatment plus rifampin or daptomycin. In the in vitro studies, tigecycline, daptomycin, and teicoplanin were active against all of the 48 Gram-positive isolates. The combination of tigecycline with rifampicin and daptomycin was synergistic against S. aureus and Enterococcus spp. In the in vivo studies, all groups treated with single drugs showed statistically significant results compared to the control group. The two groups treated with a combination of drugs showed the highest antimicrobial efficacy. In conclusion, our results suggested a strong activity of tigecycline alone and in combination with other antimicrobial agents against multi-resistant Gram-positive organisms isolated from wound infections.

Antimicrobial properties of distinctin in an experimental model of MRSA-infected wounds.

The aim of this study was to evaluate the efficacy of distinctin in the management of cutaneous methicillin-resistant Staphylococcus aureus (MRSA) wound infections in an experimental mouse model. Wounds, made in the panniculus carnosus of BALB/c mice, were inoculated with 5 × 10(7) colony-forming units (CFU) of MRSA. Mice were treated with topical distinctin (1 mg/kg of body weight), topical teicoplanin (7 mg/kg of body weight), intraperitoneal teicoplanin (7 mg/kg of body weight); topical teicoplanin and daily intraperitoneal teicoplanin; topical distinctin and daily intraperitoneal teicoplanin. Bacterial cultures of excised tissues and histological examination of microvessel density and of vascular endothelial growth factor (VEGF) expression were studied. It was found that topical distinctin combined with parenteral teicoplanin inhibited bacterial growth to levels comparable with those observed in uninfected animals. Wounded areas of animals treated with distinctin were characterized by a more mature granulation tissue, with a more organized and denser type of connective tissue, compared to mice treated only with teicoplanin. Treatment with topical distinctin had a significant impact on VEGF expression and microvessel density. The combined use of distinctin with teicoplanin may be useful in the management of infected wounds by significantly inhibiting bacterial growth and accelerating the repair process.

Social and behavioral determinants as risk of sexually transmitted diseases. Report by a sample from the Sexually Transmitted Disease Unit in Florence, Italy.

AIM: Sexually transmitted infections (STIs) are increasing worldwide, mostly due to changing sexual behavior s (larger numbers of sexual partners, concurrent relationships, increasing proportion of adolescents engaging in sexual intercourse at young age, and inconsistent condom use with new partners). In Italy, few data are available about STI spread, since most infections are not subjected to mandatory notification. METHODS: In this article, the occurrence of STIs in a random sample attending a STI Unit in Florence, Italy, is reported. Results were obtained through the administration of an anonymous questionnaire that patients could complete spontaneously in the waiting room while waiting for the visit. Self-reported questions allowed to collect information about socio-demographic and clinical data, sexual behavior and perception of risk. RESULTS: Overall, 469 patients (321 males, 148 females) participated in the study. Age ranged from 16 to 70 years. Male patients who referred to engage sexual intercourse with men (MSM) were 133; females who had sex with women (FSF) were 5, while 24 patients declared to have sex with both males and females (bisexual); 59.7% (N.=280) of participants reported they had a stable relationship, but 20% of these reported they had had sex with more than five partners during the last 12 months. The use of condoms is declared to be very infrequent, especially in the two extreme age ranges. Fifty percent of patients had been diagnosed an STI in their life, particularly syphilis (39.3%), genital warts (64.6%) and chlamydial infections (42.9%). Among those subjects who had contracted an STI (including non-curable viral infections, i.e., HIV and herpes genitalis) 32.4% referred they never used condoms. CONCLUSION: The authors discuss their results compared to the existing literature, and focus on identification of risk factors associated with self-reported STIs. Although conducted on a small population, this study provides a basis for targeting prevention and control strategies on our high-risk patients.

Creating a kidney organoid-vasculature interaction model using a novel organ-on-chip system.

Kidney organoids derived from human induced pluripotent stem cells (iPSCs) have proven to be a valuable tool to study kidney development and disease. However, the lack of vascularization of these organoids often leads to insufficient oxygen and nutrient supply. Vascularization has previously been achieved by implantation into animal models, however, the vasculature arises largely from animal host tissue. Our aim is to transition from an in vivo implantation model towards an in vitro model that fulfils the advantages of vascularization whilst being fully human-cell derived. Our chip system supported culturing of kidney organoids, which presented nephron structures. We also showed that organoids cultured on chip showed increased maturation of endothelial populations based on a colocalization analysis of endothelial markers. Moreover, we observed migration and proliferation of human umbilical vein endothelial cells (HUVECs) cultured in the channels of the chip inside the organoid tissue, where these HUVECs interconnected with endogenous endothelial cells and formed structures presenting an open lumen resembling vessels. Our results establish for the first-time vascularization of kidney organoids in HUVEC co-culture conditions using a microfluidic organ-on-chip. Our model therefore provides a useful insight into kidney organoid vascularization in vitro and presents a tool for further studies of kidney development and drug testing, both for research purposes and pre-clinical applications.

Effectiveness of antimicrobial photodynamic therapy with a single treatment of RLP068/Cl in an experimental model of Staphylococcus aureus wound infection.

BACKGROUND: Chronic leg ulceration is a common health problem. It is well known that a clinically relevant bacterial load in chronic cutaneous wounds interferes significantly with the normal process of healing. Staphylococcus aureus is the most important representative of the staphylococcal group which causes clinically relevant infections within immunocompetent patients. OBJECTIVES: To investigate the efficacy of a single treatment of antimicrobial photodynamic therapy (APDT) with RLP068/Cl in a mouse model of a surgical wound infection induced with a methicillin-resistant strain of S. aureus (MRSA). METHODS: Wounds, established through the panniculus carnosus of BALB/c and CD1 mice, were inoculated with 5 x 10(7) c.f.u. of MRSA. Mice were randomized into four groups respectively receiving no treatment, APDT with placebo, APDT with a new phthalocyanine derivative (RLP068/Cl) and intraperitoneal teicoplanin. RESULTS: On day 2 from infection, a strong reduction of bacterial counts (≈ 3 logs) was observed in mice treated with RLP068/Cl in comparison with infected untreated mice. On day 9 from infection, a comparable and significant (≈ 2 logs) reduction of bacterial counts was found in mice treated with RLP068/Cl or with teicoplanin. At this time, histological examinations revealed that wounds treated with RLP068/Cl showed a complete re-epithelialization with a continuous epithelial lining. CONCLUSIONS: The results of the in vivo study demonstrated that APDT with RLP068/Cl may be useful in the management of chronic infected wounds, accelerating the repair process through a significant bacterial inhibition.

Daptomycin and rifampin alone and in combination prevent vascular graft biofilm formation and emergence of antibiotic resistance in a subcutaneous rat pouch model of staphylococcal infection.

OBJECTIVE: To investigate the efficacy of daptomycin and rifampin either alone or in combination in preventing prosthesis biofilm in a rat model of staphylococcal vascular graft infection. DESIGN: Prospective, randomised, controlled animal study. MATERIALS: Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with 2×10(7) colony forming units of Staphylococcus aureus, strain Smith diffuse. METHODS: The study included a control group, a contaminated group that did not receive any antibiotic prophylaxis and three contaminated groups that received intra-peritoneal daptomycin, rifampin-soaked graft and daptomycin plus rifampin-soaked graft, respectively. Each group included 15 animals. The infection burden was evaluated by using sonication and quantitative agar culture. Moreover, an in vitro antibiotic susceptibility assay for S. aureus biofilms was performed to elucidate the same activity. RESULTS: When tested alone, daptomycin and rifampin showed good efficacies. Their combination showed efficacies significantly higher than that of each single compound. The in vitro studies showed that minimum inhibitory concentration and minimum bactericidal concentration values for daptomycin were lower in presence of rifampin. Daptomycin prevented the emergence of rifampin resistance. CONCLUSION: Daptomycin is an important candidate for prevention of staphylococcal biofilm-related infection and rifampin could serve as an interesting anti-staphylococcal antibiotic enhancer.

In vitro activity of the lipopeptide derivative (Pal-Lys-Lys-NH), alone and in combination with antifungal agents, against clinical isolates of dermatophytes.

BACKGROUND: An increasing number of antimycotics have become available for the treatment of dermatophytoses; however, there are reports suggesting recalcitrance to therapy or resistance of a dermatophyte against conventional treatment. Lipopeptides represent novel therapeutic drugs with a new mode of action. OBJECTIVES: The aim of this study was to investigate the in vitro effects of the lipopeptide Pal-Lys-Lys-NH(2) (PAL) alone and in combination with standard antifungal agents, such as fluconazole (FLU), itraconazole (ITRA) and terbinafine (TER) against 24 clinical isolates of dermatophytes belonging to four species. METHODS: A broth microdilution method following the Clinical and Laboratory Standards Institute recommendations (M38-A) was used for testing drugs alone and in combination. RESULTS: PAL minimum inhibitory concentrations (MICs) ranged from < or = 0.25 to > 16 microg mL(-1) and they were similar to those of FLU and higher than those of either ITRA or TER. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 67%, 52% and 15% of PAL/ITRA, PAL/TER and PAL/FLU interactions, respectively. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. CONCLUSIONS: Our study demonstrates that PAL has potential activity against dermatophytes. In addition, the in vitro activity of PAL can be enhanced upon combination with standard drugs. This lipopeptide applied in the form of lacquer, spray or ointment, could represent an interesting new therapy, particularly when combined with conventional treatment in recalcitrant or resistant dermatophyte infections.

Outcomes of the calcaneo-stop procedure for the treatment of juvenile flatfoot in young athletes.

PURPOSE: Flexible flatfoot (FFF) is a widespread condition in juvenile patients. If symptomatic, FFF can require surgical treatment. The calcaneo-stop procedure has shown excellent clinical and radiographic outcomes and low rates of complications. The aim of the present study was to assess the sport practice of young athletes affected by FFF having undergone the calcaneo-stop procedure. METHODS: Between 2008 and 2016, 68 sport practitioners were bilaterally treated by the calcaneo-stop procedure, for a total of 136 FFF cases. Clinical evaluation, including the American Orthopedic Foot and Ankle Score (AOFAS), the Yoo et al score and The Foot & Ankle Disability Index (FADI) and FADI Sport scores were assessed. Radiographic evaluation was based on measurement of talar declination, Costa-Bertani's angle and calcaneal pitch. RESULTS: Mean follow-up was 57.6 months (sd 16.8). The AOFAS score mean increased from 79.3 (sd 5.7) to 97.3 (sd 4.5) three years after surgery. The Yoo score improved from 3.1 (sd 1.0) preoperatively to 11.7 (sd 0.6) three years after surgery. The FADI Sport subscale mean improved from 74.1 (sd 10.4) preoperatively to 95.9 (sd 4.9) three years after surgery.Costa-Bertani's angle decreased from 156.1° (sd 4.2°) to 135.8° (sd 7.3°) at three years postoperatively; mean talar declination angle decreased from 44.2° (sd 6.3°) to 30.6° (sd 3.2°) at three years postoperatively and mean calcaneal pitch increased from 12.6° (sd 2.3°) to 16.3° (sd 1.3°) at three years postoperatively. CONCLUSION: Adolescent patients who underwent the calcaneo-stop procedure reported satisfactory outcomes in terms of clinical and radiological evaluations. Moreover, our results showed an improvement of sport activity levels, with patients recovering sports activity within three months of surgery and without limitation in the execution of preferred activities. LEVEL OF EVIDENCE: IV.

Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips.

We present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 µm in diameter and a wide porosity range (2-65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 µm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs.

Coding sequence and intron-exon junctions of the c-myb gene are intact in the chronic phase and blast crisis stages of chronic myeloid leukemia patients.

The c-myb gene encodes a transcription factor required for proliferation, differentiation and survival of normal and leukemic hematopoietic cells. c-Myb has a longer half-life in BCR/ABL-expressing than in normal cells, a feature which depends, in part, on PI-3K/Akt-dependent regulation of proteins interacting with the leucine zipper/negative regulatory region of c-Myb. Thus, we asked whether the stability of c-Myb in leukemic cells might be enhanced by mutations interfering with its degradation. We analyzed the c-myb gene in 133 chronic myeloid leukemia (CML) patients in chronic phase and/or blast crisis by denaturing-high performance liquid chromatography (D-HPLC) and sequence analysis of PCR products corresponding to the entire coding sequence and each exon-intron boundary. No mutations were found. We found four single nucleotide polymorphisms (SNPs) and identified an alternatively spliced transcript lacking exon 5, but SNPs frequency and expression of the alternatively spliced transcript were identical in normal and CML cells. Thus, the enhanced stability of c-Myb in CML blast crisis cells and perhaps in other types of leukemia is not caused by a genetic mechanism.

In-vitro activity of the synthetic protegrin IB-367 alone and in combination with antifungal agents against clinical isolates of Candida spp.

The in vitro activity of the peptide IB-367, alone or combined with either fluconazole (FLU) or amphotericin B (AMB), was investigated against 25 Candida isolates belonging to five species. IB-367 minimum inhibitory concentrations (MICs) ranged from 2.0 to 32 microg/ml and it was active against both FLU-susceptible and - resistant isolates. A rapid fungicidal activity was observed. Synergism was documented in 41.6% and 44% of IB-367/FLU and IB-367/AMB interactions, respectively. Antagonism was never observed. The broad antifungal activity and the positive interactions with AMB and FLU suggest that IB-367 represents a promising candidate against infections due to Candida spp.

Genetic improvement of olive (Olea europaea L.) by conventional and in vitro biotechnology methods.

In olive (Olea europaea L.) traditional methods of genetic improvement have up to now produced limited results. Intensification of olive growing requires appropriate new cultivars for fully mechanized groves, but among the large number of the traditional varieties very few are suitable. High-density and super high-density hedge row orchards require genotypes with reduced size, reduced apical dominance, a semi-erect growth habit, easy to propagate, resistant to abiotic and biotic stresses, with reliably high productivity and quality of both fruits and oil. Innovative strategies supported by molecular and biotechnological techniques are required to speed up novel hybridisation methods. Among traditional approaches the Gene Pool Method seems a reasonable option, but it requires availability of widely diverse germplasm from both cultivated and wild genotypes, supported by a detailed knowledge of their genetic relationships. The practice of "gene therapy" for the most important existing cultivars, combined with conventional methods, could accelerate achievement of the main goals, but efforts to overcome some technical and ideological obstacles are needed. The present review describes the benefits that olive and its products may obtain from genetic improvement using state of the art of conventional and unconventional methods, and includes progress made in the field of in vitro techniques. The uses of both traditional and modern technologies are discussed with recommendations.

A combined CoMFA and CoMSIA 3D-QSAR study of benzamide type antibacterial inhibitors of the FtsZ protein in drug-resistant Staphylococcus aureus.

A major problem today is bacterial resistance to antibiotics and the small number of new therapeutic agents approved in recent years. The development of new antibiotics capable of acting on new targets is urgently required. The filamenting temperature-sensitive Z (FtsZ) bacterial protein is a key biomolecule for bacterial division and survival. This makes FtsZ an attractive new pharmacological target for the development of antibacterial agents. There have been several attempts to develop ligands able to inhibit FtsZ. Despite the large number of synthesized compounds that inhibit the FtsZ protein, there are no quantitative structure-activity relationships (QSAR) that allow for the rational design and synthesis of promising new molecules. We present the first 3D-QSAR study of a large and diverse set of molecules that are able to inhibit the FtsZ bacterial protein. We summarize a set of chemical changes that can be made in the steric, electrostatic, hydrophobic and donor/acceptor hydrogen-bonding properties of the pharmacophore, to generate new bioactive molecules against FtsZ. These results provide a rational guide for the design and synthesis of promising new antibacterial agents, supported by the strong statistical parameters obtained from CoMFA (r(2)(pred) = 0.974) and CoMSIA (r(2)(pred) = 0.980) analyses.

Role of the endocannabinoid system in obesity induced by neuropeptide Y overexpression in noradrenergic neurons.

OBJECTIVE: Endocannabinoids and neuropeptide Y (NPY) promote energy storage via central and peripheral mechanisms. In the hypothalamus, the two systems were suggested to interact. To investigate such interplay also in non-hypothalamic tissues, we evaluated endocannabinoid levels in obese OE-NPY(DßH) mice, which overexpress NPY in the noradrenergic neurons in the sympathetic nervous system and the brain. METHODS: The levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were measured in key regulatory tissues, that is, hypothalamus, pancreas, epididymal white adipose tissue (WAT), liver and soleus muscle, over the development of metabolic dysfunctions in OE-NPY(DßH) mice. The effects of a 5-week treatment with the CB1 receptor inverse agonist AM251 on adiposity and glucose metabolism were studied. RESULTS: 2-AG levels were increased in the hypothalamus and epididymal WAT of pre-obese and obese OE-NPY(DßH) mice. Anandamide levels in adipose tissue and pancreas were increased at 4 months concomitantly with higher fat mass and impaired glucose tolerance. CB1 receptor blockage reduced body weight gain and glucose intolerance in OE-NPY(DßH) to the level of vehicle-treated wild-type mice. CONCLUSIONS: Altered endocannabinoid tone may underlie some of the metabolic dysfunctions in OE-NPY(DßH) mice, which can be attenuated with CB1 inverse agonism suggesting interactions between endocannabinoids and NPY also in the periphery. CB1 receptors may offer a target for the pharmacological treatment of the metabolic syndrome with altered NPY levels.